It is estimated that over 90% of all drugs used to produce a systemic effect are administered by the oral route. Of all drugs that are administered orally, solid oral dosage forms represent the preferred class of product. These oral tablet dosage forms include several benefits: they are a unit dose form, offering the least content variability, they are inexpensive, they are the lightest and most compact of all oral dosage forms, they are the easiest and cheapest to package and ship, product identification is simple and cheap, they have greatest ease of swallowing especially when coated, they easily lend themselves to certain special-release profile products such as enteric or delayed-release products, they are better suited to large-scale production, and have the best combined properties of chemical, mechanical and microbiologic stability of all oral forms. Another important consideration is that the tablets are relatively tamper resistant.
The tableting process generally includes compressing various formulations into a compact unit by means of a tablet press. A tablet press using a punch and die set is traditionally used and can produce large amounts of tablets in a short period of time.
Compressed tablet formulations currently are produced by using one of three general methods: wet granulation; double compaction (dry granulation); or direct compression. Direct compression involves only the mixing and compression of a formulation. Despite its ease and lesser cost due to less processing time and energy involved, direct compression is rarely used because very few substances exhibit good flow and compaction.
Wet granulation is currently the most widely used method. This process binds powders together with an adhesive instead of compaction. The technique involves incorporation of binder solution, slurry or suspension into the powder mixture while mixing or the binder may be incorporated into the powder mixture and subsequently wetted while mixing and then compressed.
The dry granulation method involves the initial compaction of a formulation into slugs by means of flat-faced punches or roller compactors. The slugs are then screened or milled into granules for tableting.
Very few active medicaments will flow freely, directly compress, or are dosed at strengths that make the tablet easily handled for oral administration. It is often necessary to incorporate other products into a formulation to improve stability, aid in manufacture and aid in performance of the dosage form. These ingredients (excipients) must be nontoxic, must not be contraindicated themselves (such as sucrose or sodium) and must be physiologically inert, physically and chemically stable by themselves and in combination with drugs, and finally they must have no deleterious effect on bioavailability of the drugs. Tablet preparation additives include bulking agents, binding agents, lubricants, gildants, disintegrants, coloring agents and flavoring agents.
Probably one of the most important excipients are binding agents that impart particle cohesiveness to the tablet formulation which insures that the tablet will remain intact after compression. Further, granulating with binders may improve the free flowing qualities of a formulation which is needed to pass through a high speed tablet press. Materials commonly used as binders include starch, gelatin, and sugars such as sucrose, glucose, dextrose, molasses, and lactose. Natural and synthetic gums also have been used including acacia, sodium alginate, carboxymethylcellulose, methylcellulose and polyvinylpyrrolidone. Other agents which may be considered binders under certain circumstances include polyethylene glycol, ethylcellulose and some waxes. Binders may be used in solution or in the dry form depending on the other ingredients in the formulation and method of preparation. The proper binder/solvent system must be selected to obtain the desired properties for a tablet.
As can be seen, a continuing need exists in the art for new excipients which may be used in solid oral dose form pharmaceutical preparations. This invention relates to the use of spray dried animal plasma as an excipient for tablet pharmaceutical formulations. Spray dried animal plasma exhibits the properties of a good binder as well as properties for a direct compression vehicle and a sustained release vehicle, the latter two uses include novel uses for protein substances.
It is an object of the present invention to provide a protein excipient which is cost effective and which may be used in pharmaceutical compositions.
A further object of the present invention is directed to the use of spray dried animal plasma as a tablet binder.
Another object of the present invention is to provide a method of preparation of pharmaceutical tablets.
Yet another object of the present invention is to provide a protein excipient which may be used as a direct compression vehicle and a sustained release vehicle.
A further object of the present invention is to provide a tablet binder which maintains tablet integrity, is chemically inert, and will sustain prolonged drug release.
Further objects of the invention will become obvious from the detailed description of the invention which follows.